Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
Authors: Audrey Y Jung, Thomas U Ahearn, Sabine Behrens, Pooja Middha, Manjeet K Bolla, Qin Wang, Volker Arndt, Kristan J Aronson, Annelie Augustinsson, Laura E Beane Freeman, Heiko Becher, Hermann Brenner, Federico Canzian, Lisa A Carey, Kamila Czene, A Heather Eliassen, Mikael Eriksson, D Gareth Evans, Jonine D Figueroa, Lin Fritschi, Marike Gabrielson, Graham G Giles, Pascal Guénel, Andreas Hadjisavvas, Christopher A Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Reiner Hoppe, John L Hopper, Anthony Howell, David J Hunter, Anika Hüsing, Rudolf Kaaks, Veli-Matti Kosma, Stella Koutros, Peter Kraft, James V Lacey, Loic Le Marchand, Jolanta Lissowska, Maria A Loizidou, Arto Mannermaa, Tabea Maurer, Rachel A Murphy, Andrew F Olshan, Håkan Olsson, Alpa V Patel, Charles M Perou, Gad Rennert, Rana Shibli, Xiao-Ou Shu, Melissa C Southey, Jennifer Stone, Rulla M Tamimi, Lauren R Teras, Melissa A Troester, Thérèse Truong, Celine M Vachon, Sophia S Wang, Alicja Wolk, Anna H Wu, Xiaohong R Yang, Wei Zheng, Alison M Dunning, Paul D P Pharoah, Douglas F Easton, Roger L Milne, Nilanjan Chatterjee, Marjanka K Schmidt, Montserrat García-Closas, Jenny Chang-Claude
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. Methods Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. Results Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity &amp;lt; .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity &amp;lt; .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. Conclusions This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.